The release of neurotransmitters from presynaptic nerve terminals by the fusion of transmitter-filled secretory vesicles with the nerve terminal membrane is critical for the transfer of information throughout the nervous system. This release is gated by the influx of calcium ions via voltage-gated ion channels and the control of channel availability is a major mechanism in the control of synaptic strength, and hence, synaptic pathways. We are exploring the function of these calcium channels by several different approaches. We are examining the role of Ca channels in the presynaptic nerve terminal using the giant presynaptic terminal of the chick ciliary ganglion as an experimental model. Our main findings have been the characterization of the K channels that are activated by Ca influx at single channel and whole cell levels by direct recording from the nerve terminal. These findings demonstrate that the KCa channels exhibit characteristics consistent with playing a major role in the defining of the duration of the action potential and that they can be activated by the plume of Ca that enters through nearby clustered Ca channels. Second, we have examined the mechanisms whereby calcium ions are extruded from the nerve terminal by localizing the calcium pumps and the sodium-calcium exchangers. Contrary to expectations, the exchangers are at locations that are distant from the transmitter release sites whereas the pumps are at the release sites themselves. Finally, we have demonstrated that activation of presynaptic Ca channels results in a depletion of Ca ions in the synaptic cleft - a phenomenon that has been proposed on the basis of theoretical studies but has not been observed directly. This ion cleft depletion may be the underlying reason why transmitter release sites are of a characteristic structure and supports the idea that Ca influx is minimized through the presynaptic membrane during transmitter release. - presynaptic, transmitter release, calcium channel, potassium channel, nerve terminal, autonomic, cholinergic, chick